COPD: preclinical models and emerging therapeutic targets

ABSTRACT

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Preclinical models of COPD have recently been developed. In those models, COPD/emphysema has been commonly induced using different toxic agents such as elastase, proteolytic enzymes and chronic exposure to cigarette smoke (CS).

Areas covered: The most relevant features of preclinical models of COPD, namely chronic exposure to CS and other agents (proteases and microorganisms), cardiovascular effects, surfactant protein-D, airway remodeling and inflammation, lung regeneration potential and mesenchymal stromal cell therapy are described. The most relevant publications on the topic of interest were selected from Pubmed.

Expert opinion: Preclinical models of COPD are key for understanding the underlying biology and pathophysiology of the disease and for the discovery of therapeutic targets. Enhanced biological insights will help discover therapeutic targets for the treatment of COPD. This will enable health caregivers and doctors to improve treatment where a more holistic approach will be used. This will benefit the patients and society because the use of resources should be significantly lowered.

KEYWORDS:

• Animal models
• cigarette smoke exposure
• COPD
• lung regeneration potential
• mesenchymal stromal cells
• surfactant protein-D

Article highlights

• Cigarette smoke exposure is a relevant model of COPD to study the respiratory system and other organs

• Proteases (elastase) and microorganisms or microbial components are useful models of COPD to study exacerbations

• Cardiovascular manifestations are major comorbidities in COPD and may be studied using specific animal models

• Animal models of surfactant protein-D help elucidate the role of this protein in COPD

• Mouse models of airway remodeling are relevant to shed light into this biological process in COPD

• Therapeutic strategies based on the use of mesenchymal stromal cells look promising in the near-future as evidenced from animal models

• Preclinical models of COPD are key elements for the design of therapeutic targets: lungs and airways and the extra-pulmonary manifestations of the disease

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer is an employee and shareholder of GlaxoSmithKline. One referee receives grants and personal fees from Verona Pharma and has patents licensed to Verona Pharma. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

In the last five years, the group of the author has received funds from Center of Investigation in Respiratory Disease (CIBERES); FIS 14/00713 (FEDER); FIS 18/00075 (FEDER); SEPAR 2016; SEPAR 2018; FUCAP 2016; Unrestricted grant from Menarini SA 2018 (Spain), and GlaxoSmithKline SA (Spain) 2018.